Fluorescent dyes and nanoparticles are widely used in chemistry, biology, and medicine but suffer from poor photostability or toxicity (nanoparticles). The goal of this proposal is to create ultra-stable, monovalent, organic nanoparticles or organic coated metallic/silicon nanoparticles (< 6 nm size) using recently discovered chemistry that allows polyglycerol dendrimers and hyperbranched polymers to be tightly cross-linked around a core structure. The polyglycerol surfaces will be allylated and cross-linked using the ring-closing metathesis (RCM) reaction, followed by surface dihydroxylation to create a water-soluble particle. This chemistry is colloquially referred to as multi-layer shrink-wrapping. The goal of the shrink-wrapping is to chemically isolate the fluorophore or preexisting nanoparticle and thus: (1) prevent dye aggregation, which often diminishes its performance, (2) prevent its undesired association with membranes and other biomolecules, and, most importantly, (3) reduce or eliminate photobleaching, and (4) stabilize existing nanoparticles with a dense, biocompatible sheath. We propose that through extreme isolation of the fluorophore or nanoparticle it may function indefinitely, thereby enabling a range of applications not previously possible. The fluorescent nanoparticles, which are designed to be fully biocompatible, can exhibit a range of excitation and emission wavelengths. PUBLIC HEALTH RELEVANCE: Fluorescent dyes and nanoparticles are widely used in medical diagnostics and for understanding chemical and biological processes at the molecular and cellular level. However, the dyes degrade rapidly upon irradiation and many nanoparticles contain toxic metals or are inherently toxic because of their surface coating. We propose a new strategy for preparing organic-based, ultra-stable and biocompatible fluorescent nanoparticles.